The economic impact of machine perfusion technology in liver transplantation

Introduction: Several clinical studies have demonstrated the safety, feasibility, and efficacy of machine perfusion in liver transplantation, although its economic outcomes are still underexplored. This review aimed to examine the costs related to machine perfusion and its associated outcomes.Methods: Expert opinion of several groups representing different machine perfusion modalities. Critical analysis of the published literature reporting the economic outcomes of the most used techniques of machine perfusion in liver transplantation (normothermic and hypothermic ex situ machine perfusion and in situ normothermic regional perfusion).Results: Machine perfusion costs include disposable components of the perfusion device, perfusate components, personnel and facility fees, and depreciation of the perfusion device or device lease fee. The limited current literature suggests that although this upfront cost varies between perfusion modalities, its use is highly likely to be cost-effective. Optimization of the donor liver utilization rate, local conditions of transplant programs (long waiting list times and higher MELD scores), a decreased rate of complications, changes in logistics, and length of hospital stay are potential cost savings points that must highlight the expected benefits of this intervention. An additional unaccounted factor is that machine perfusion optimizing donor organ utilization allows patients to be transplanted earlier, avoiding clinical deterioration while on the waiting list and the costs associated with hospital admissions and other required procedures.Conclusion: So far, the clinical benefits have guided machine perfusion implementation in liver transplantation. Albeit there is data suggesting the economic benefit of the technique, further investigation of its costs to healthcare systems and society and associated outcomes is needed.</p

Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High-Risk Livers Using Normothermic Machine Perfusion

Increased use of high-risk allografts is critical to meet the demand for liver transplantation. We aimed to identify criteria predicting viability of organs, currently declined for clinical transplantation, using functional assessment during normothermic machine perfusion (NMP). Twelve discarded human livers were subjected to NMP following static cold storage. Livers were perfused with a packed red cell-based fluid at 37°C for 6 hours. Multilevel statistical models for repeated measures were employed to investigate the trend of perfusate blood gas profiles and vascular flow characteristics over time and the effect of lactate-clearing (LC) and non-lactate-clearing (non-LC) ability of the livers. The relationship of lactate clearance capability with bile production and histological and molecular findings were also examined. After 2 hours of perfusion, median lactate concentrations were 3.0 and 14.6 mmol/L in the LC and non-LC groups, respectively. LC livers produced more bile and maintained a stable perfusate pH and vascular flow &gt;150 and 500 mL/minute through the hepatic artery and portal vein, respectively. Histology revealed discrepancies between subjectively discarded livers compared with objective findings. There were minimal morphological changes in the LC group, whereas non-LC livers often showed hepatocellular injury and reduced glycogen deposition. Adenosine triphosphate levels in the LC group increased compared with the non-LC livers. We propose composite viability criteria consisting of lactate clearance, pH maintenance, bile production, vascular flow patterns, and liver macroscopic appearance. These have been tested successfully in clinical transplantation. In conclusion, NMP allows an objective assessment of liver function that may reduce the risk and permit use of currently unused high-risk livers.</p

Discarded livers tested by normothermic machine perfusion in the VITTAL trial:Secondary end points and 5-year outcomes

Normothermic machine perfusion (NMP) enables pretransplant assessment of high-risk donor livers. The VITTAL trial demonstrated that 71% of the currently discarded organs could be transplanted with 100% 90-day patient and graft survivals. Here, we report secondary end points and 5-year outcomes of this prospective, open-label, phase 2 adaptive single-arm study. The patient and graft survivals at 60 months were 82% and 72%, respectively. Four patients lost their graft due to nonanastomotic biliary strictures, one caused by hepatic artery thrombosis in a liver donated following brain death, and 3 in elderly livers donated after circulatory death (DCD), which all clinically manifested within 6 months after transplantation. There were no late graft losses for other reasons. All the 4 patients who died during the study follow-up had functioning grafts. Nonanastomotic biliary strictures developed in donated after circulatory death livers that failed to produce bile with pH &gt;7.65 and bicarbonate levels &gt;25 mmol/L. Histological assessment in these livers revealed high bile duct injury scores characterized by arterial medial necrosis. The quality of life at 6 months significantly improved in all but 4 patients suffering from nonanastomotic biliary strictures. This first report of long-term outcomes of high-risk livers assessed by normothermic machine perfusion demonstrated excellent 5-year survival without adverse effects in all organs functioning beyond 1 year (ClinicalTrials.gov number NCT02740608).</p

The economic impact of machine perfusion technology in liver transplantation.

INTRODUCTION Several clinical studies have demonstrated the safety, feasibility, and efficacy of machine perfusion in liver transplantation, although its economic outcomes are still underexplored. This review aimed to examine the costs related to machine perfusion and its associated outcomes. METHODS Expert opinion of several groups representing different machine perfusion modalities. Critical analysis of the published literature reporting the economic outcomes of the most used techniques of machine perfusion in liver transplantation (normothermic and hypothermic ex situ machine perfusion and in situ normothermic regional perfusion). RESULTS Machine perfusion costs include disposable components of the perfusion device, perfusate components, personnel and facility fees, and depreciation of the perfusion device or device lease fee. The limited current literature suggests that although this upfront cost varies between perfusion modalities, its use is highly likely to be cost-effective. Optimization of the donor liver utilization rate, local conditions of transplant programs (long waiting list times and higher MELD scores), a decreased rate of complications, changes in logistics, and length of hospital stay are potential cost savings points that must highlight the expected benefits of this intervention. An additional unaccounted factor is that machine perfusion optimizing donor organ utilization allows patients to be transplanted earlier, avoiding clinical deterioration while on the waiting list and the costs associated with hospital admissions and other required procedures. CONCLUSION So far, the clinical benefits have guided machine perfusion implementation in liver transplantation. Albeit there is data suggesting the economic benefit of the technique, further investigation of its costs to healthcare systems and society and associated outcomes is needed

Retrieval Practice or Overall Donor and Recipient Risk: What Impacts on Outcomes After Donation After Circulatory Death Liver Transplantation in the United Kingdom?

Parameters of retrieval surgery are meticulously documented in the United Kingdom, where up to 40% of livers are donation after circulatory death (DCD) donations. This retrospective analysis focuses on outcomes after transplantation of DCD livers, retrieved by different UK centers between 2011 and 2016. Donor and recipient risk factors and the donor retrieval technique were assessed. A total of 236 DCD livers from 9 retrieval centers with a median UK DCD risk score of 5 (low risk) to 7 points (high risk) were compared. The majority used University of Wisconsin solution for aortic flush with a median hepatectomy time of 27-44 minutes. The overall liver injury rate appeared relatively high (27.1%) with an observed tendency toward more retrieval injuries from centers performing a quicker hepatectomy. Among all included risk factors, the UK DCD risk score remained the best predictor for overall graft loss in the multivariate analysis (P < 0.001). In high-risk and futile donor-recipient combinations, the occurrence of liver retrieval injuries had negative impact on graft survival (P = 0.023). Expectedly, more ischemic cholangiopathies (P = 0.003) were found in livers transplanted with a higher cumulative donor-recipient risk. Although more biliary complications with subsequent graft loss were found in high-risk donor-recipient combinations, the impact of the standardized national retrieval practice on outcomes after DCD liver transplantation was minimal

Avaliação do colesterol plasmático em coelhos com hipercolesterolemia induzida e tratados com extrato etanólico de própolis

The propolis (bee glue) is a product rich in flavonoids, which are known for antioxidant activities, a protective action to the lipoproteins LDL-cholesterol against lipid peroxidation. Because they have antioxidant properties, we investigated the effect of the ethanolic extract propolis on the plasma level of cholesterol in rabbits (Oryctolagus cuniculus) submitted to hypercholesterolaemia. The animals were divided into 4 groups. G 1=received commercial feed and water, G 2=received enriched feed and water, G 3=received enriched feed and ethanol, G 4=received enriched feed and ethanolic extract of propolis. The hypercholesterolaemia was induced with commercial feed enriched with egg yolk. The animals received the ethanolic extract propolis at the concentration of 100 mg/kg daily. Weekly, after fast of 14 hours, the samples of blood were collected from the marginal vein of the ear. The plasma was used for the estimation total cholesterol. From the results obtained, we verified that the ethanolic extract propolis significantly reduced the plasma level cholesterol (109,59 mg/dL, p<0,05), compared to the animals treated with ethanol (331,38 mg/dL), and also to those receiving the commercial feed only, with cholesterol at 269,74 mg/dL

Comparative study of the mandarin hybrid fruit characteristics: Nova, Murcott and Ortanique in Capão Bonito SP, Brazil Estudo comparativo das características dos frutos dos híbridos de tangerina: Nova, Murcott e Ortanique, na região de Capão Bonito, SP

The Murcott tangor represent 20% of the tangerines trees in São Paulo State being the second more grown. Their fruits have good acceptance in the market cause of the good characteristics presented as: size, attractive internal and external color, transport resistance, high juice rate and industry potential. It is necessary to study the behavior of others varieties, in order to amplify the diversity of tangerine industry, which show suitable characteristics to the fresh fruit market and that make possible different harvest season. Many tangerine varieties, selected from the Citrus Germplasm Bank of the do Centro Avançado de Pesquisa Tecnológica do Agronegócio de Citros "Sylvio Moreira"/IAC, belong to trials carried out in 15 places in São Paulo State. The Capão Bonito area, south-west of the state, is one of this places where the Nova tangelo, the Ortanique and the Murcott tangors are showing quite good results about their fruit qualities. This paper had as an objective to compare the fruit characteristics of the Nova tangelo, the Murcott and the Ortanique tangors grafted on two rootstocks: Rangpur lime and Cleopatra mandarin. Accordingly to the gotten results, is possible to conclude that Nova and Ortanique had shown weight, width, fruit shape and juice percent, similar to the Murcott. In compliance with the harvest season, the Nova present suitable conditions to fresh fruit market in May and June. By the other hand the Murcott fruits can be harvested in July to August and the Ortanique in August to September. For this reason, is possible extend the harvest season of this mandarin-like, from two to five month, occurring inclusive in a period out of the crop at the north hemisphere.<br>O tangor Murcott representa 20% das tangerinas plantadas no Estado de São Paulo, sendo a segunda mais cultivada. Seus frutos têm excelente aceitação no mercado por apresentar boas características como tamanho adequado para o consumidor, coloração alaranjada forte tanto de casca quanto de polpa, resistência ao transporte, alto rendimento de suco e potencial para industrialização. Há necessidade de estudar o comportamento de outras variedades, para ampliar a diversidade da cultura da tangerina, que apresentem adequadas características para o mercado de fruta fresca e que possibilitem diferentes épocas de colheita. Diversas variedades de tangerinas, pré-selecionadas no Banco Ativo de Germoplasma de Citros, do Centro Avançado de Pesquisa Tecnológica do Agronegócio de Citros "Sylvio Moreira"/IAC/APTA fazem parte de experimentos conduzidos em 15 localidades do Estado de São Paulo. A região de Capão Bonito, situada no sudoeste paulista, constitui um dos locais onde o tangelo Nova e os tangores Murcott e Ortanique vêm apresentando resultados bastante satisfatórios quanto à qualidade de seus frutos. Avaliou-se neste trabalho, as características físico-químicas do tangelo Nova e dos tangores Murcott e Ortanique nos porta-enxertos limão Cravo e tangerina Cleópatra. Nova e Ortanique apresentaram valores de massa, diâmetro e forma do fruto e rendimento de suco, semelhantes aos do tangor Murcott. Quanto ao período de colheita, os frutos da variedade Nova apresentaram condições adequadas para consumo em maio e junho, já os frutos de Murcott podem ser colhidos em julho e agosto e a Ortanique em agosto e setembro. Assim sendo, há possibilidade de estender o período de safra desse grupo de tangerina, de dois para cinco meses, vindo inclusive a ocorrer num período de entressafra no hemisfério norte